REGULATION OF ACETYL CoA PROCESSING

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BIOC 460 DR. TISCHLER LECTURE 37
REGULATION OF ACETYL CoA PROCESSING
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OBJECTIVES

• Regulation of processes in the formation of
  acetyl CoA
• a) describe regulation of
  hormone-sensitive lipase by covalent
  modification
• b) mechanism by which activators or
  inhibitors of phospho- diesterase affect
  activity of hormone-sensitive lipase
•  
• Regulation of processes in the utilization of
  acetyl CoA
• a) factors that induce (increase) or
  repress (decrease) synthesis of acetyl CoA
  carboxylase and FAS
• b) events associated with
  polymerization-depolymerization describe of
  acetyl CoA carboxylase
• c) events associated with covalent modification
  of acetyl CoA carboxylase
• d) induction of HMG CoA reductase through
  mRNA production in the presence of low
  cholesterol.
• e) events associated with covalent
  modification of HMG-CoA reductase
• 3. Drugs that inhibit HMG-CoA reductase to lower
  cholesterol

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LIPOLYSIS

• Mobilization of fats from triacylglycerols
• Regulated step hormone sensitive lipase
• Specific for removing first fatty acid
• Phosphorylated a form is active
• Dephosphorylated b form is inactive

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cell membrane
HORMONES
Epinephrine Glucagon
Adenylyl cyclase


protein kinase A
inactive
active
RECEPTORS
Phospho- diesterase

activation
-
inhibition

Figure 1. Hormonal activation of triacylglycerol
(hormone-sensitive) lipase. Hormone signals from
epinephrine or glucagon promote mobilization of
fatty acids (lipolysis) via production of cyclic
AMP. Activated protein kinase A, phosphorylates
HSL-b to the active HSL-a form .
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Table 1. Long-term control by induction or
repression of acetyl CoA carboxylase and fatty
acid synthase
PHYSIOLOGICAL CONDITION EFFECT
High-carbohydrate, low-fat diet ?
synthesis High-fat diet ? synthesis Fasting
? synthesis
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Figure 2a. Regulation of acetyl CoA carboxylase
by citrate and palmitoyl CoA via polymerization
and depolymerization
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Figure 2b. Regulation of acetyl CoA carboxylase
by glucagon, epinephrine and insulin
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Reversing the inactivation of acetyl CoA
carboxylase
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Reversing the inactivation of acetyl CoA
carboxylase
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High Cholesterol
SREBP, sterol regulatory element binding protein
NUCLEUS
Low Cholesterol
ENDOPLASMIC RETICULUM
synthesis of HMG CoA reductase
mRNA for HMG CoA Reductase
Figure 3. HMG CoA reductase is induced when
intracellular cholesterol becomes too low while
with high cholesterol SREBP is bound to the
endoplasmic reticulum and is thus rendered
ineffective
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Figure 4. Inactivation of HMG CoA reductase by
phosphorylation in response to glucagon or
epinephrine
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Figure 4. Activation of HMG CoA reductase by
dephosphorylation in response to insulin
RK
(active)
ADP
OPO3
RKK
(active)
ATP
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